US4393201A - DNA Which codes for glycoprotein of era-strain rabies virus - Google Patents
DNA Which codes for glycoprotein of era-strain rabies virus Download PDFInfo
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- US4393201A US4393201A US06/318,315 US31831581A US4393201A US 4393201 A US4393201 A US 4393201A US 31831581 A US31831581 A US 31831581A US 4393201 A US4393201 A US 4393201A
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2760/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses negative-sense
- C12N2760/00011—Details
- C12N2760/20011—Rhabdoviridae
- C12N2760/20111—Lyssavirus, e.g. rabies virus
- C12N2760/20122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
Definitions
- This invention relates to rabies virus, more particularly, the ERA-strain of rabies virus. Most particularly, this invention relates to DNA which carries the code for the glycoprotein of the ERA-strain rabies virus.
- Rabies RNA virus is a rhabdovirus which has a single (non-segmented) negative-strand RNA genome which is transcribed upon infection to produce five polyadenylated complementary monocistronic mRNA species.
- Each of the virus-specific mRNA's representing a structural gene of the rabies virus genome codes for a virion structural protein which corresponds in size to the apparent coding capacity of its mRNA (see Pennica, et al., Virology, 103, 517-521 (1980); and Wunner, et al., J. Virol. 36, 133-142 (1980)).
- the glycoprotein RNA gene codes for a membrane-associated molecule which forms spike-like projections on the surface of mature rabies virions and is responsible for the induction and binding of virus-neutralizing antibodies to rabies virus (see Wiktor, et al., J. Immun. 110, 269-276 (1973); Cox, et al., Infect. Immun. 16, 754-759 (1977); and Dietzschold, et al., J. gen. Virol. 40, 131-139 (1978)).
- rabies glycoprotein is the primary antigen in rabies virus, it is expected that eventually, injection of the glycoprotein or segments of the glycoprotein which contain an antigen site into an animal will prove to be an effective immunological procedure, without the inherent risks associated with immunization of a patient with denatured rabies virus.
- Rabies viruses isolated from different animal species in various parts of the world were in the past considered to be closely related by serological tests.
- several rabies-related viruses see Shope, et al., J. Virol. 6, 690-692 (1970); and Tignor, et al., J. gen. Virol. 37, 595-611 (1977)), isolated mainly from bats and considered to belong to the same genus as rabies virus within the family Rhabdoviridae, have shown more distant serological relatedness to each other and to rabies viruses (Fenner, F. Intervirology 7, 42-43 (1976)).
- a DNA is provided which is a copy of the glycoprotein mRNA of ERA-strain rabies virus.
- This glycoprotein specific single-strand DNA contains an initiation codon (ATG) and a termination codon (TGA).
- FIG. 1 illustrates the results of hybridization analysis of rabies virus surface glycoprotein polyA RNA and rabies virus nucleocapsid protein polyA RNA from rabies virus-infected cells.
- FIG. 2 illustrates the sites at which various restriction enzymes cleave rabies glycoprotein specific DNA.
- FIGS. 3 illustrates the complete cDNA nucleotide and corresponding predicted amino acid sequences of the ERA strain rabies glycoprotein.
- the entire cDNA sequence of the coding portion of the glycoprotein gene in ERA-strain rabies virus has been characterized.
- a cDNA copy of the glycoprotein mRNA sequence has been cloned into pBR322 plasmid in order to define the antigenic and immunogenic properties of rabies virus glycoprotein.
- polyA RNA was isolated by oligo-dT cellulose chromatography from total RNA extracted from rabies virus-infected cells. Selection of rabies glycoprotein mRNA was achieved in size selection (sucrose gradient). The polyA RNA ranging from 15-20S was identified by the ability of the samples to direct synthesis of glycoprotein in micro-injected oocytes. Cloning of rabies virus-specific genes M 1 , M 2 and L was excluded because the M 1 and M 2 proteins are synthesized by smaller mRNA's (about 12S) and the L protein is synthesized by a much larger mRNA (greater than about 28S).
- NC nucleocapsid protein
- the isolated polyA RNA was converted into double-strand complementary DNA and AMV reverse transcriptase and E. coli DNA polymerase I. Following digestion with S 1 nuclease and tailing with dCMP residues, DNA larger than 1 kilobase pairs was selected by sucrose gradient centrifugation. The selected DNA was hybridized with dG-tailed pBR322 prior to transformation of E. coli x1776. Tetracycline-resistant colonies were screened using 32 P-labeled rabies virion RNA. Approximately one percent of the colonies responded to the probe with varying intensities. Of 100 colonies that were rescreened, 20 colonies were selected that gave the strongest signals from the probe.
- Single-strand cDNA was prepared in a 400 ul-volume reaction containing 20 ug 15-20S polyA RNA from cells infected with the ERA strain of rabies virus, 50 nM (millimolar) Tris-HCl (pH 8.3), 35 mM KCl, 10 mM MgCl 2 , 30 mM ⁇ -mercaptoethanol, 20 uCi 3 H-dCTP (17 Ci/mmol, ICN), 0.5 mM dATP, dCTP, dGTP, dTTP, 200 ug/ml BSA and 150 units of AMV reverse transcriptase. The reaction mixture was incubated at 42° C. for 60 minutes.
- the cDNA (6 ug) was purified by phenol extraction and Sephadex G100 chromatography. Double-strand cDNA was synthesized in a reaction volume of 400 ul containing 25 mM Tris-HCl (pH 8.3), 70 mM KCl, 5 mM MgCl 2 , 16 mM ⁇ -mercaptoethanol, 100 mM Hepes buffer (pH 6.9)., 50 uCi 32 P ⁇ -dCTP (400 Ci/mmol, Amersham), 0.1 mM dCTP, 0.5 mM dATP, dGTP, dTTP, and 12.5 units of E. coli DNA polymerase I (Boehringer Mannheim).
- Double-strand cDNA (5 ug) purified from the reaction as above was treated with S 1 nuclease (4000 units (Miles) in 0.25 M NaCl, 0.03 M sodium acetate (pH 4.5), and 1 mM ZnCl 2 ), at 37° C. for 45 minutes.
- the DNA (2 ug) was elongated with dCMP residues in 160 ul containing 0.1 M sodium cacodylate (pH 7.0), 2.5 mM CoCl 2 , 150 uM dCTP, 50 ug/ml BSA and 48 units of terminal deoxynucleotide transferase (University of Zurich) by incubation at 0° C. for 30 minutes.
- Purified dC-tailed double-strand cDNA was fractionated according to size by sedimentation in a 5-23% sucrose gradient and centrifugation at 49,000 rpm for 5 hours at 10° C. in a SW65 rotor.
- the annealed mixture yielded approximately 1000 tetracycline-resistant colonies upon transformation of E. coli x1776 (Villa-komaroff et al, Proc. Nat. Acad. Sci. U.S.A. 75, 3727-3731 (1978)). Tetracycline-resistant colonies were grown for 48 hours on agar plates before transferring them to Whatman No. 540 filters.
- the filters were prepared as described by Grunstein and Hogness, Proc. Nat. Acad. Sci. U.S.A. 72, 3961-3965 (1975), (except for an initial treatment with 0.2 N HCl for 20 minutes) and hybridized in 50% formamide (Alwine et al, Proc. Nat. Acad. Sci.
- rabies virion RNA was partially degraded by heating at 55° C. for 50 minutes in 0.05 M Na 2 CO 3 , neutralized by adjustment to 0.3 M sodium acetate (pH 5.5), and precipitated with ethanol.
- the partially degraded RNA (1 ug) was labeled by inclubation in 50 mM Tris-HCl (pH 8.0 ), 10 mM MgCl 2 , 10 mM dithiothreitol, 50 uCi ⁇ - 32 P-ATP (about 5,000 Ci/mmol, Amersham) with 10 units of polynucleotide kinase (PL Biochemicals) at 37° C. for 60 minutes.
- Plasmids from the 20 colonies selected above were checked for their size by digestion with BamH I to give linear molecules, and with Pst I to excise the cDNA insert.
- the BamH I- and Pst I- restricted plasmid DNA's containing rabies virus gene sequences were electrophoresced on 1% and 1.5% agarose gels, respectively.
- a plasmid was chosen from each group for further analysis: A344 which contained an insert having an estimated 1.75 kilobase pairs and lacking any additional BamH I site, and B333 which contained an insert having an estimated 1.3 kilobase pairs and having an additional BamH I site.
- the inserts of A344 and B333 were isolated by Pst I digestion and electrophoresis on 1.5% agarose, gel (Tabak and Flavell, Nucl. Acid Res. 5, 2321-2332 (1978)).
- Each insert was then labeled by nick-translation (Rigby, et al., J. mol. Biol. 113, 237-251 (1977)) and hybridized to individual fractions of polyA RNA derived from rabies virus-infected cells, and sedimented in a sucrose gradient.
- the labeled probes were heated at 100° C. for 5 minutes, adjusted to 50% formamide, 0.75 M NaCl, 10 mM Hepes buffer (pH 6.8), 1 mM EDTA, 1 mg/ml yeast RNA, and then heated with fractionated polyA RNA from rabies virus-infected cells in a total volume of 10 ul at 45° C. for 16 hours under paraffin oil. Hybridization was terminated by addition of cold 0.25 M NaCl, 0.03 M sodium acetate (pH 4.5), and 1 mM ZnCl 2 . After removal of paraffin oil, S 1 nuclease (100 units) was added and the solution was incubated at 37° C. for 45 minutes. Acid-insoluble counts were determined by TCA precipitation.
- PolyA RNA (about 130 ug) was heat-denatured at 100° C. for 1 minute and centrifuged in a 5-23% sucrose gradient at 25,000 rpm at 10° C. for 16 hours in a Beckman SW41 rotor. Each fraction (0.5 ml) from the gradient was diluted 1:60 with water and 1 ul was hybridized with labeled probe (about 3,000 cpm, specific activity 10 8 cpm/ug).
- the insert of plasmid A344 hybridized to an mRNA sedimenting at 18S, the location of maximum mRNA activity for the synthesis of glycoprotein, while the insert of plasmid B333 hybridized to an mRNA sedimenting at 16S, the location of mRNA capable of directing the synthesis in oocytes of nucleocapsid protein.
- the plasmids A344 and B333 were designated as pRG (glycoprotein) and pRN (nucleocapsid protein), respectively.
- the complete nucleotide sequence of the glycoprotein cDNA was determined by a technique using both 5'- and 3'- labeled restriction fragments defined by the sites indicated in FIG. 2 (Maxam and Gilbert, Meth. Enzym. 65, 499-560 (1980)).
- FIG. 2 shows the restriction map of the insert of pRG.
- an oligo-dG:dC tract of 24 residues is present while near the opposite end there is an oligo-dG:dC tract of 14 residues.
- These tracts were added onto the cDNA in the tailing process preparatory to annealing with pBR322.
- a sequence of polydA designated (A)n in FIG. 2 which exists in the clone as two lengths of approximately 50 and 80 base pairs.
- boxes designate the initiation codon (ATG) and the termination codon (TGA).
- the initiation codon (ATG) is located at nucleotides 8-10 from the 5'-end of the clone.
- the other two reading frames contain numerous stop codons, such that the longest polypeptide which can be derived from them is less than 50 amino acids long.
- Numbers in parenthesis in FIG. 3 designate the numerical sequence of amino acids counted from the N-terminal lysine residue of the mature glycoprotein which is located 20 amino acids from the initiation codon (ATG).
- the first six amino acid residues of the mature glycoprotein (lys - phe - pro - ile - tyr - thr -), have been identified independently by direct N-terminal amino acid sequence analysis of purified rabies virus (ERA strain) glycoprotein.
- the sequence of amino acids is located 20-25 residues from the initiating methionine codon in the deduced sequence.
- the deduced amino acid composition of the mature rabies virus (ERA strain) glycoprotein (residues per molecule) is shown in Table II.
- the determined sequence codes for a protein of 524 amino acids including a signal peptide of 19 nonpolar acids preceding the amino-terminal lysine residue of the mature glycoprotein.
- the signal polypeptide is normally associated with a transmembrane protein (Lingappa et al, J. biol. Chem. 253, 8667-8670 (1978)) and is removed during maturation of the polypeptide.
- the amino acid residues in the structure of rabies glycoprotein cDNA shown in FIG. 3 have accordingly been numbered beginning with the N-terminal lysine of the mature glycoprotein.
- a relatively long sequence of 44 charged and uncharged residues extends from the putative transmembrane polypeptide domain to the carboxy-terminal leucine codon at position 505.
- the deduced amino acid sequence contains four carbohydrate acceptor sites as defined by the sequence (asn-X-ser) and (asn-X-thr). Three of these sites are located on the N-terminal side of the putative transmembrane segment in the ERA-glycoprotein cDNA. Three carbohydrate chains have been found on the rabies virus glycoprotein of the ERA strain (Dietzschoid, B. J. Virol. 23, 286-293 (1977)) in agreement with the predicted number of carbohydrate attachment sites excluding the fourth carbohydrate acceptor site at positions 465-467 (which is within the putative transmembrane domain).
- Restriction mapping established the size of the inserted cDNA of pRG as approximately 1.75 kilobase pairs (see FIG. 2).
- a small primer fragment located close to the 5'-end of the glycoprotein sequence and bounded by the restriction sites for Pvu II and Hind III was labeled and hybridized to 18S polyA RNA from rabies virus-infected cells. Incubation of the hybrid formed between the glycoprotein mRNA and the labeled cDNA fragment with AMV reverse transcriptase extended the primer fragment to the 5' terminus of the glycoprotein mRNA. Products of the reaction were resolved on a denaturing gel and identified by autoradiography.
- the glycoprotein gene sequence was restricted with Pvu II, labeled by ⁇ - 32 P-ATP with polynucleotide kinase, and subsequently digested with Hind III.
- the resulting labeled fragment consisting of 36 base pairs was isolated on a 5% polyacrylamide (0.1% bis-acrylamide) gel in 50 mM Tris-borate (pH 8.3), 1 mM EDTA, eluted and dried.
- the 32 P-labeled fragment was then denatured in 20 ul of 80% (volume/volume) formamide by heating at 100° C. for 3 minutes.
- a sample of 18S polyA RNA (10 ug) from rabies virus-infected cells was dried with 20 ul of solution containing 0.4 M NaCl, 20 mM Hepes buffer (pH 6.8), and 1 mM EDTA (pH 7.5).
- the solution of denatured 32 P-labeled DNA was added to the dried RNA and incubated successively at 60° C., 58° C., 56° C., and 54° C. for 1 hour at each temperature. After annealing, the mixture was transferred into 100 ul cold 0.3 M sodium acetate (pH 5.5) and precipitated by 2.5 volumes of ethanol at -20° C.
- the precipitated nucleic acids were dissolved in 40 ul of 50 mM Tris-HCl (pH 8.3), 10 mM MgCl 2 , 35 mM KCl, 30 mM ⁇ -mercaptoethanol, 0.5 mM each of the four deoxynucleoside triphosphates, 200 ug/ml BSA, 12.5 ug/ml actinomycin D and AMV reverse transcriptase (12 units), and incubated at 37° C. for 90 minutes.
- nucleic acids were dissolved in 4 ul 80% formamide, 50 mM Tris-borate (pH 8.3), 1 mM EDTA, 0.1% xylene cyanol FF and 0.1% bromophenol blue and heated at 90° C. for 1 minute before loading onto an 8% polyacrylamide (0.4% bis-acrylamide) gel containing 50% (weight/volume) urea, 100 mM Tris-borate (pH 8.3), and 2 mM EDTA. Labeled nucleic acids were detected by autoradiography using an intensifying screen at -70° C.
- the major products were approximately 40 and 165 nucleotides in length. Products having 40 nucleotides presumably arose by filling in the Hind III site recreated by the annealing of Pvu II-Hind III DNA strands, while the products having 165 nucleotides resulted from the extension of the primer which was hybridized to glycoprotein mRNA.
- the inserted rabies glycoprotein cDNA sequence contains approximately 1.69 kilobase pairs.
- the operative features of the glycoprotein cDNA are contained between the initiation codon (ATG) and the termination codon (TGA), as shown in FIG. 3.
- This sequence which contains the coding sequence for the glycoprotein, begins at the initiating methionine, and includes the signal sequence which consists of the first 19 codons after the initiation (ATG) codon.
- ATG initiation codon
- TGA termination codon
- the ERA strain of rabies virus contains a single glycoprotein form with a molecular weight of approximately 67,000, while within the cell there exists a smaller form which has a molecular weight of about 63,000 (as determined by polyacrylamide gel analysis).
- This smaller form of glycoprotein which lacks most of the carbohydrate of the mature form comprises at most 570 amino acids (average molecular weight 110), compatible with the deduced size of 505 residues for the mature glycoprotein.
- Virus-neutralizing anti-glycoprotein monoclonal antibodies have been used to select virus variants which no longer can be neutralized by single monoclonal antibodies used for selection. Presumably, an amino acid change is responsive for the altered antibody binding sites.
- the cloned glycoprotein cDNA may be used to prepare primers for DNA synthesis on parent and variant virion RNA as templates in order to compare the nucleotide sequences between parent and variant viruses. Computer analysis of the sequences can be used to predict exposed antigenic regions on the virion glycoprotein.
- the cloned glycoprotein cDNA is treated by appropriate restriction enzymes and separation techniques to select for a primer sequence which is located near but not within the bounds of an antigenic site or proposed antigenic site.
- the resulting primer is then hybridized to glycoprotein mRNA or virion RNA from a suspected variant rabies virus strain.
- a cDNA for the variant in the region of the antigenic site is produced by treating the cDNA primer-hybridized mRNA or virion RNA with AMV reverse transcriptase (using the techniques earlier discussed). Differences in the product cDNA sequence as compared with the ERA-strain cDNA sequence may then be mapped by determining the new cDNA sequence using techniques already discussed above.
- the cDNA of the rabies virus and variant glycoprotein mRNAs may be used to transform bacteria so that an antigenic polypeptide is produced in quantities sufficient for use in immunization.
- the antigenic polypeptide may be synthesized in vitro for use in immunization.
Abstract
Description
TABLE I ______________________________________ A. Nucleotides A = adenine G = guanine C = cytosine T = thymine B. Amino acids Full Name Abbreviation Full Name Abbreviation ______________________________________ Alanine Ala Leucine Leu Arginine Arg Lysine Lys Asparagine Asn Methionine Met Aspartic acid Asp Phenylalanine Phe Cysteine Cys Proline Pro Glutamic acid Glu Serine Ser Glutamine Gln Threonine Thr Glycine Gly Tryptophan Trp Histidine His Tyrosine Tyr Isoleucine Ile Valine Val ______________________________________
TABLE II ______________________________________ Residues Per Residues Per Amino acid Molecule Amino acid Molecule ______________________________________Alanine 20 Leucine 51Arginine 28Lysine 28 Asparagine 21 Methionine 13 Aspartic acid 25 Phenylalanine 18 Cysteine 16Proline 28 Glutamic acid 31 Serine 42 Glutamine 8 Threonine 34 Glycine 38 Tryptophan 9 Histidine 18 Tyrosine 16 Isoleucine 22 Valine 39 ______________________________________
Claims (1)
Priority Applications (3)
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US06/318,315 US4393201A (en) | 1981-11-04 | 1981-11-04 | DNA Which codes for glycoprotein of era-strain rabies virus |
FR8218495A FR2515685B1 (en) | 1981-11-04 | 1982-11-04 | DNA ENCODING FOR GLYCOPROTEIN OF ERA STRAIN VIRUS |
DE19823240748 DE3240748A1 (en) | 1981-11-04 | 1982-11-04 | DNA CODING FOR GLYCOPROTEIN FROM ERA-STREAM RABBIT VIRUS AND METHOD FOR THEIR PRODUCTION |
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US06/318,315 US4393201A (en) | 1981-11-04 | 1981-11-04 | DNA Which codes for glycoprotein of era-strain rabies virus |
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Cited By (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4562159A (en) * | 1981-03-31 | 1985-12-31 | Albert Einstein College Of Medicine, A Division Of Yeshiva Univ. | Diagnostic test for hepatitis B virus |
WO1987000179A1 (en) * | 1985-07-03 | 1987-01-15 | The Salk Institute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US4689320A (en) * | 1983-10-17 | 1987-08-25 | Akira Kaji | Method for inhibiting propagation of virus and anti-viral agent |
US4707356A (en) * | 1985-07-03 | 1987-11-17 | The Salk Institute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US4743553A (en) * | 1984-07-18 | 1988-05-10 | W. R. Grace & Co. | Synthetic genes for bovine parainfluenza virus |
US5041370A (en) * | 1984-05-02 | 1991-08-20 | The Upjohn Company | Pseudorabies virus (PRV) gene, host cell, method for detecting animals infected with pseudorabies virus, and kit therefor |
US5066593A (en) * | 1985-07-03 | 1991-11-19 | The Salk Insstitute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US5698202A (en) * | 1995-06-05 | 1997-12-16 | The Wistar Institute Of Anatomy & Biology | Replication-defective adenovirus human type 5 recombinant as a rabies vaccine carrier |
US5830477A (en) * | 1984-04-25 | 1998-11-03 | Transgene S.A. | Vaccine against rabies and process for preparation thereof |
US6019978A (en) * | 1995-06-05 | 2000-02-01 | The Wistar Institute Of Anatomy And Biology | Replication-defective adenovirus human type 5 recombinant as a vaccine carrier |
US6024953A (en) * | 1984-04-25 | 2000-02-15 | Transgene S.A. | Vaccine against rabies and process for preparation thereof |
US6210663B1 (en) | 1998-08-20 | 2001-04-03 | The Wistar Institute Of Anatomy And Biology | Methods of augmenting mucosal immunity through systemic priming and mucosal boosting |
US7238672B1 (en) * | 2000-04-17 | 2007-07-03 | Institut Pasteur | Chimeric lyssavirus nucleic acids and polypeptides |
US20080274130A1 (en) * | 2005-10-14 | 2008-11-06 | The Govt. Of The U.S.A. As Represented By The Secretary Of The Dept.Of Health And Human Services | Rabies Virus Vector Systems and Compositions and Methods Thereof |
US9217158B2 (en) | 2008-03-14 | 2015-12-22 | Sanofi Pasteur Biologics, Llc | Replication-defective flavivirus vaccines and vaccine vectors |
US20210353735A1 (en) * | 2018-09-07 | 2021-11-18 | Katholieke Universiteit Leuven | Chimeric Flavivirus Lyssavirus Vaccines |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1985001516A1 (en) * | 1983-10-03 | 1985-04-11 | Transgene S.A. | Vectors for the expression of an antigenic protein of rabies in eucaryotic cells and application thereof to the preparation of a vaccine |
FR2552776B1 (en) * | 1983-10-03 | 1986-05-09 | Transgene Sa | VECTORS FOR THE EXPRESSION OF AN ANTIGENIC PROTEIN OF RABIES IN EUKARYOTIC CELLS AND THEIR APPLICATION TO THE PREPARATION OF A VACCINE |
EP0237686A1 (en) * | 1986-03-18 | 1987-09-23 | Institut Pasteur | DNA sequences derived from the rabies virus genome |
JPH01171489A (en) * | 1987-12-26 | 1989-07-06 | Chemo Sero Therapeut Res Inst | Gene fragment coding glycoprotein of rabies virus and production of rabies virus glycoprotein using said fragment |
-
1981
- 1981-11-04 US US06/318,315 patent/US4393201A/en not_active Expired - Lifetime
-
1982
- 1982-11-04 FR FR8218495A patent/FR2515685B1/en not_active Expired
- 1982-11-04 DE DE19823240748 patent/DE3240748A1/en active Granted
Non-Patent Citations (9)
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
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US4562159A (en) * | 1981-03-31 | 1985-12-31 | Albert Einstein College Of Medicine, A Division Of Yeshiva Univ. | Diagnostic test for hepatitis B virus |
US4689320A (en) * | 1983-10-17 | 1987-08-25 | Akira Kaji | Method for inhibiting propagation of virus and anti-viral agent |
US6024953A (en) * | 1984-04-25 | 2000-02-15 | Transgene S.A. | Vaccine against rabies and process for preparation thereof |
US5830477A (en) * | 1984-04-25 | 1998-11-03 | Transgene S.A. | Vaccine against rabies and process for preparation thereof |
US5041370A (en) * | 1984-05-02 | 1991-08-20 | The Upjohn Company | Pseudorabies virus (PRV) gene, host cell, method for detecting animals infected with pseudorabies virus, and kit therefor |
US4743553A (en) * | 1984-07-18 | 1988-05-10 | W. R. Grace & Co. | Synthetic genes for bovine parainfluenza virus |
WO1987000179A1 (en) * | 1985-07-03 | 1987-01-15 | The Salk Institute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US4652629A (en) * | 1985-07-03 | 1987-03-24 | The Salk Institute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US4707356A (en) * | 1985-07-03 | 1987-11-17 | The Salk Institute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US5066593A (en) * | 1985-07-03 | 1991-11-19 | The Salk Insstitute For Biological Studies | Synthetic peptide-based anti-rabies compositions and methods |
US6019978A (en) * | 1995-06-05 | 2000-02-01 | The Wistar Institute Of Anatomy And Biology | Replication-defective adenovirus human type 5 recombinant as a vaccine carrier |
US5698202A (en) * | 1995-06-05 | 1997-12-16 | The Wistar Institute Of Anatomy & Biology | Replication-defective adenovirus human type 5 recombinant as a rabies vaccine carrier |
US6287571B1 (en) | 1995-06-05 | 2001-09-11 | The Wistar Institute Of Anatomy And Biology | Replication-defective adenovirus human type 5 recombinant as a vaccine carrier |
US6210663B1 (en) | 1998-08-20 | 2001-04-03 | The Wistar Institute Of Anatomy And Biology | Methods of augmenting mucosal immunity through systemic priming and mucosal boosting |
US7238672B1 (en) * | 2000-04-17 | 2007-07-03 | Institut Pasteur | Chimeric lyssavirus nucleic acids and polypeptides |
US20080274130A1 (en) * | 2005-10-14 | 2008-11-06 | The Govt. Of The U.S.A. As Represented By The Secretary Of The Dept.Of Health And Human Services | Rabies Virus Vector Systems and Compositions and Methods Thereof |
US7863041B2 (en) | 2005-10-14 | 2011-01-04 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services, Centers For Disease Control And Prevention | Rabies virus vector systems and compositions and methods thereof |
US8865461B2 (en) | 2005-10-14 | 2014-10-21 | The United States of America as represtented by the Secretary of the Department of Health and Human Services, Centers for Disease Control and Prevention | Rabies virus vector systems and compositions and methods thereof |
US9217158B2 (en) | 2008-03-14 | 2015-12-22 | Sanofi Pasteur Biologics, Llc | Replication-defective flavivirus vaccines and vaccine vectors |
US20210353735A1 (en) * | 2018-09-07 | 2021-11-18 | Katholieke Universiteit Leuven | Chimeric Flavivirus Lyssavirus Vaccines |
Also Published As
Publication number | Publication date |
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DE3240748C2 (en) | 1991-09-12 |
FR2515685B1 (en) | 1985-10-25 |
DE3240748A1 (en) | 1983-05-19 |
FR2515685A1 (en) | 1983-05-06 |
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